This grant deals with elastin, calcification and vitamin K-dependent calcium binding proteins in cardiovascular and pulmonary tissues. Its rationale suggests that lesions or nectrotic events involving cells leads to the accumulations of lipids at or around elastin fibers. The environment established and an inflammatory stimulus causes the migration of progenitor cells to the site, followed by their subsequent differentiation into calcium mobilizing cells which can carry out vitamin K-dependent, Gamma-carboxyglutamate-containing protein synthesis. This pathological process is essentially a severe distortion of a process related to normal endochondral bone formation. This grant examines the temperal and topological relationships between elastin, Gla-proteins such as atherocalcin, and the vitamin K-dependent carboxylations in cardiovascular pulmonary tissues. Another aspect of the elastin research deals with what may turn out to be a new genetic type of elastin synthesized in elastic cartilage by condrocytes. Elastin crosslinking is also examined in normal and pathological human tissues and in various tissues from animal models which show pathological changes involving calcium accumulation and Gla-synthesis.